脑淀粉样血管病核心 CSF 生物标志物谱：更新的荟萃分析。

Core CSF Biomarker Profile in Cerebral Amyloid Angiopathy: Updated Meta-Analysis.

机构信息

From the Department of Neurology (A.C.), Boston University Medical Center, Boston University School of Medicine, MA; and Diagnostic and Interventional Neuroradiology (G.B.), University Hospital, Tours, France.

出版信息

Neurology. 2024 Oct 8;103(7):e209795. doi: 10.1212/WNL.0000000000209795. Epub 2024 Sep 13.

DOI:10.1212/WNL.0000000000209795

PMID:39270153

Abstract

BACKGROUND AND OBJECTIVES

There is a clear need to characterize and validate molecular biomarkers of cerebral amyloid angiopathy (CAA), in an effort to improve diagnostics, especially in the context of patients with Alzheimer disease (AD) receiving immunotherapies (for whom underlying CAA is the driver of amyloid-related imaging abnormalities). We performed an updated meta-analysis of 5 core CSF biomarkers (Aβ42, Aβ40, Aβ438, total tau [T-tau], and phosphorylated tau [P-tau]) to assess which of these are most altered in sporadic CAA.

METHODS

We systematically searched PubMed for eligible studies reporting data on CSF biomarkers reflecting APP metabolism (Aβ42, Aβ40, Aβ38), neurodegeneration (T-tau), and tangle pathology (P-tau), in symptomatic sporadic CAA cohorts (based on the Boston criteria) vs control groups and/or vs patients with AD. Biomarker performance was assessed in random-effects meta-analysis based on ratio of mean (RoM) biomarker concentrations in (1) patients with CAA to controls and (2) CAA to patients with AD. RoM >1 indicates higher biomarker concentration in CAA vs comparison population, and RoM <1 indicates higher concentration in comparison groups.

RESULTS

8 studies met inclusion criteria: a total of 11 CAA cohorts (n = 289), 9 control cohorts (n = 310), and 8 AD cohorts (n = 339). Overall included studies were of medium quality based on our assessment tools. CAA to controls had lower mean level of all amyloid markers with CSF Aβ42, Aβ40, and Aβ38 RoMs of 0.46 (95% CI 0.38-0.55, < 0.0001), 0.70 (95% CI 0.63-0.78, < 0.0001), and 0.71 (95% CI 0.56-0.89, = 0.003), respectively. CSF T-tau and P-tau RoMs of patients with CAA to controls were both greater than 1: 1.56 (95% CI 1.32-1.84, < 0.0001) and 1.31 (95% CI 1.13-1.51, < 0.0001), respectively. Differentiation between CAA and AD was strong for CSF Aβ40 (RoM 0.76, 95% CI 0.69-0.83, < 0.0001) and Aβ38 (RoM 0.55, 95% CI 0.38-0.81, < 0.0001), but not Aβ42 (RoM 1.00; 95% CI 0.81-1.23, = 0.970). For T-tau and P-tau, average CSF ratios in patients with CAA vs AD were 0.64 (95% CI 0.58-0.71, < 0.0001) and 0.64 (95% CI 0.58-0.71, < 0.0001), respectively.

DISCUSSION

Specific CSF patterns of Aβ42, Aβ40, Aβ38, T-tau, and P-tau might serve as molecular biomarkers of CAA, in research and clinical settings, offering the potential to improve the clinical diagnostic approach pathway in specific scenarios.

摘要

背景与目的

需要对脑淀粉样血管病（CAA）的分子生物标志物进行特征描述和验证，以提高诊断水平，特别是在接受免疫治疗的阿尔茨海默病（AD）患者中（这些患者的潜在 CAA 是淀粉样相关成像异常的驱动因素）。我们对 5 种核心 CSF 生物标志物（Aβ42、Aβ40、Aβ438、总 tau [T-tau] 和磷酸化 tau [P-tau]）进行了更新的荟萃分析，以评估这些生物标志物在散发性 CAA 中的改变程度。

方法

我们系统地在 PubMed 上搜索了符合条件的研究报告，这些研究报告提供了反映 APP 代谢（Aβ42、Aβ40、Aβ38）、神经退行性变（T-tau）和缠结病理（P-tau）的 CSF 生物标志物数据，这些数据来自基于波士顿标准的有症状散发性 CAA 队列（与对照组和/或 AD 患者相比）。基于平均比值（RoM）生物标志物浓度的随机效应荟萃分析评估了生物标志物的性能，该比值是在（1）CAA 患者与对照组之间和（2）CAA 患者与 AD 患者之间的比值。RoM >1 表示 CAA 与比较人群相比，生物标志物浓度更高，而 RoM <1 表示比较组中浓度更高。

结果

共有 8 项研究符合纳入标准：共 11 个 CAA 队列（n = 289）、9 个对照组（n = 310）和 8 个 AD 队列（n = 339）。根据我们的评估工具，总体纳入研究的质量为中等。CAA 与对照组相比，所有淀粉样标志物的平均水平均较低，CSF Aβ42、Aβ40 和 Aβ38 的 RoM 分别为 0.46（95%CI 0.38-0.55， < 0.0001）、0.70（95%CI 0.63-0.78， < 0.0001）和 0.71（95%CI 0.56-0.89， = 0.003）。CAA 与对照组相比，CSF T-tau 和 P-tau 的 RoM 均大于 1：1.56（95%CI 1.32-1.84， < 0.0001）和 1.31（95%CI 1.13-1.51， < 0.0001）。CSF Aβ40（RoM 0.76，95%CI 0.69-0.83， < 0.0001）和 Aβ38（RoM 0.55，95%CI 0.38-0.81， < 0.0001）对 CAA 与 AD 的区分能力较强，但 Aβ42 则不然（RoM 1.00；95%CI 0.81-1.23， = 0.970）。对于 T-tau 和 P-tau，CAA 患者与 AD 患者的平均 CSF 比值分别为 0.64（95%CI 0.58-0.71， < 0.0001）和 0.64（95%CI 0.58-0.71， < 0.0001）。